New Technical and Conceptual Advances in Neuro-Vascular Coupling

The laboratory discovered the world's first artery-specific fluorescent dye—Alexa 633 hydrazide (see Panel A). In much of our past work, we ignored the cerebral microvasculature, assuming that they had a necessary but permissive role in neural function. However, we recently observed remarkable dynamics of arteriole dilation in the cerebral cortex to patterned visual stimulation. This was only possible via discovery of a fluorescent dye that selectively labels arterioles in vivo. This dye does not label veins, astrocytes, and neurons. We determined the binding site of the dye on the arteriole wall. The artery-specific dye can be applied locally in the brain via a micropipette or intravenously. Any excess dye that does not ‘stick’ to the arteriole wall is rapidly cleared from the bloodstream (with intravenous application) or the cerebrospinal fluid (with local intra-cortical application). We also used the dye to detect a previously unknown artifact when neuronal calcium imaging is being performed. More recently, we determined the precise spatial scale over which neural and vascular signals are correlated in the visual cortex. We measured sensory-evoked responses of individual blood vessels (dilation, blood velocity) while imaging synaptic and spiking activity in the surrounding tissue using fluorescent glutamate and calcium sensors. We generated tuning curves for individual vessel responses for the first time and found that parenchymal vessels were orientation selective (see Panel B). However, synaptic and spiking responses were more selective than vascular responses—vessels frequently responded robustly to stimuli that evoked little to no neural activity in the surrounding tissue (see Panel C). Thus, local neural and haemodynamic signals were partly decoupled. Together, these results indicate that intrinsic cortical properties, such as propagation of vascular dilation between neighbouring columns, need to be accounted for when decoding haemodynamic signals.